A computational approach to design a polyvalent vaccine against human respiratory syncytial virus.

Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups-a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Blueprint of epitope-based multivalent and multipathogenic vaccines: targeted against the dengue and zika viruses.

Both dengue virus (DENV) and zika virus (ZIKV) belong to the highly infectious Flaviviridae family that has already caused several outbreaks and epidemics in many countries. DENV and ZIKV cause two of the most wide spread mosquito-borne viral diseases in the world, dengue fever (DENF) and zika fever (ZIKF), respectively. In many regions around the world, both of these diseases can outbreak together and can be lethal as well as life-threatening. Unfortunately, there is no functional and satisfactory vaccine available to combat these viruses. Therefore, in this study, we have attempted to design a blue print of potential multivalent and multipathogenic vaccines using immunoinformatics approach, which can combat both the DENV and ZIKV infections, simultaneously. Initially, three vaccines were designed; containing highly antigenic, non-allergenic, and non-toxic epitopes of T-cell (100% conserved) and B-cell from all the four DENV serotypes and ZIKV. In total, nine cytotoxic T-lymphocytic (CTL), nine helper T-lymphocytic (HTL), and seven B-cell lymphocytic (BCL) epitopes were used to construct three vaccines using three different adjuvants, designated as 'V1', 'V2', and 'V3'. Later, V3 was found to be the best vaccine construct, determined by molecular docking analysis. Thereafter, several in silico validation studies including molecular dynamics simulation and immune simulation were performed which indicated that V3 might be quite stable and should generate substantial immune response in the biological environment. However, further in vivo and in vitro validation might be required to finally confirm the safety and efficacy of our suggested vaccine constructs.Communicated by Ramaswamy H. Sarma.

Designing novel epitope-based polyvalent vaccines against herpes simplex virus-1 and 2 exploiting the immunoinformatics approach.

Herpes Simplex Virus (HSV) is a highly infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV exist i.e. HSV-1 and HSV-2, that are infecting millions of people around the world. However, no satisfactory treatment or counter-measure has yet been discovered to fight against the HSV infections. In this study, three possible polyvalent subunit vaccines against multiple strains of HSV-1 and HSV-2, targeting the envelope glycoproteins- E, B, and D, were designed using the tools of reverse vaccinology and immunoinformatics. The highly antigenic, non-allergenic, non-toxic, non-homolog (to the human proteome), and 100% conserved epitopes across the selected strains and species (eight epitopes from each of the CTL, HTL, and BCL epitope groups), were selected for vaccine construction. These designed vaccines are expected to be effective against the selected viral types simultaneously (as a polyvalent vaccine), without producing any unwanted adverse reaction within the body. Finally, from the three vaccine constructs, one best vaccine was determined by molecular docking analysis and thereafter, the MD simulation and immune simulation studies of the best vaccine construct also yielded satisfactory results, pointing towards quite good stability of the complex. Finally, in silico cloning was performed for analyzing the effective mass production strategy of the best vaccine construct. However, wet lab-based study should be conducted on the suggested vaccines for validating their potentiality, safety, and efficacy.Communicated by Ramaswamy H. Sarma.